Early life epigenetics and childhood outcomes: a scoping review.

Epigenetics is the study of changes in gene expression, without a change in the DNA sequence that are potentially heritable. Epigenetic mechanisms such as DNA methylation, histone modifications, and small non-coding RNA (sncRNA) changes have been studied in various childhood disorders. Causal links to maternal health and toxin exposures can introduce epigenetic modifications to the fetal DNA, which can be detected in the cord blood. Cord blood epigenetic modifications provide evidence of in-utero stressors and immediate postnatal changes, which can impact both short and long-term outcomes in children. The mechanisms of these epigenetic changes can be leveraged for prevention, early detection, and intervention, and to discover novel therapeutic modalities in childhood diseases. We report a scoping review of early life epigenetics, the influence of maternal health, maternal toxin, and drug exposures on the fetus, and its impact on perinatal, neonatal, and childhood outcomes. IMPACT STATEMENT: Epigenetic changes such as DNA methylation, histone modification, and non-coding RNA have been implicated in the pathophysiology of various disease processes. The fundamental changes to an offspring's epigenome can begin in utero, impacting the immediate postnatal period, childhood, adolescence, and adulthood. This scoping review summarizes current literature on the impact of early life epigenetics, especially DNA methylation on childhood health outcomes.

Diagnostic Accuracy of Urinary N Terminal pro-B Type Natriuretic Peptides for Hemodynamically Significant-Patent Ductus Arteriosus in Preterm Infants.

BACKGROUND: Echocardiography is the gold standard for the diagnosis hemodynamically significant-patent ductus arteriosus (hs-PDA). It requires trained personnel and is not readily available. Urinary biomarkers can be used as an adjunct. OBJECTIVE: The objective of this study was to systematically review the diagnostic accuracy of urinary N terminal pro-B type natriuretic peptides (NT-proBNP) for hs-PDA in preterm neonates. METHODS: We included studies that evaluated urinary NT-proBNP and urinary NT-proBNP/creatinine ratio (index tests) in preterm neonates with hs-PDA (participants) in comparison with echocardiogram (reference standard). Methodological quality and certainty of evidence were assessed using Quality Assessment of Diagnostic-Accuracy Studies (QUADAS-2) and Grading of Recommendations Assessment, Development and Evaluation (GRADE), respectively. RESULTS: Low quality of evidence suggests that urinary NT-proBNP has modest sensitivity and specificity for the diagnosis of a hs-PDA, with variation in accuracy based on assay and patient characteristics. CONCLUSION: Urinary NT-proBNP assays must be locally validated for specific patient populations and further studies to support its use must be performed.

Oxygen saturation index: an adjunct for oxygenation index in congenital diaphragmatic hernia.

OBJECTIVE: Our objective was to investigate the correlation of Oxygen Saturation Index (OSI) with Oxygenation Index (OI) and determine OSImax values that could predict need for ECMO and death in Congenital Diaphragmatic Hernia (CDH). STUDY DESIGN: This is a retrospective cohort study of infants with CDH admitted to a tertiary level VI NICU. Pearson's correlation coefficient and simple linear regression analysis were used to investigate the OSI: OI correlation, and logistic regression analysis to investigate OSImax values that predicted need for ECMO and death. RESULTS: Among the 180 infants, OSImax value of >13 at 6 h of life (HOL) best predicted need for ECMO and death. There was a strong correlation between OSI: OI paired values (r = 0.876, p < 0.001). The linear regression equation was OI = -2.4 + 2.4(OSI). CONCLUSION: OSI could be used as a valuable adjunct to OI in the clinical management of newborn infants with CDH.

Inotropic score and vasoactive inotropic score as predictors of outcomes in congenital diaphragmatic hernia: A single center retrospective study.

Background: Neonates with congenital diaphragmatic hernia (CDH) have varying degrees of pulmonary hypoplasia, pulmonary hypertension (PH) and cardiac dysfunction. These neonates frequently require vasoactive support and are at high risk for mortality and morbidity, including prolonged ventilator support, need for extracorporeal membrane oxygenation (ECMO), prolonged length of stay, and need for tracheostomy. However, identifying which infants are at increased risk can be challenging. In this study, we sought to investigate the utility of the inotropic score (IS) and vasoactive inotropic score (VIS) as tools to predict significant clinical outcomes and overall survival in patients with CDH. Additionally, we evaluated the correlation between IS/VIS and postnatal echocardiographic variables. Methods: This was a retrospective chart review of 57 patients with CDH whose postnatal care was based on a standardized institutional protocol. We calculated the IS/VIS at 6-, 12-, 24-, 48 hours of life (HOL), on the day of CDH repair and 24- and 48 hours after surgical repair. The association of these scores with postnatal echocardiographic markers was analyzed using Pearson's correlation and linear regression, while logistic regression was used for binary outcomes, and Cox proportional hazards regression was used to assess associations with survival. Results: We found that every one-unit increase in IS/VIS at 6 HOL was associated with 13% increase in the odds of ECMO (p = 0.034) and 10.1% increase in risk of death (p = 0.021). An increase in IS/VIS at 12-, 24- and 48-HOL was associated with posterior septal bowing in the first postnatal echocardiogram (p < 0.05 for all). Additionally, we noted an inverse relationship between IS (r = -0.281, p = 0.036) and VIS (r = -0.288, p = 0.031) on the day of repair and left ventricle (LV) systolic function in first postnatal echocardiogram. Increase in IS (r = -0.307, p = 0.024) and VIS (r = -0.285, p = 0.037) on the day of repair was associated with decreased LV function on the post-repair echocardiogram. Conclusion: This retrospective study showed a significant association between IS/VIS obtained at various time points with clinical outcomes and echocardiographic findings in CDH, which could be used to guide prognosis and management in this patient population.

Use of Prostaglandin E1 in the Management of Congenital Diaphragmatic Hernia-A Review.

Congenital diaphragmatic hernia (CDH) is a rare congenital anomaly, whose presentation is complicated by pulmonary hypertension (PH), pulmonary hypoplasia, and myocardial dysfunction, each of which have significant impact on short-term clinical management and long-term outcomes. Despite many advances in therapy and surgical technique, optimal CDH management remains a topic of debate, due to the variable presentation, complex pathophysiology, and continued impact on morbidity and mortality. One of the more recent management strategies is the use of prostaglandin E1 (PGE1) infusion in the management of PH associated with CDH. PGE1 is widely used in the NICU in critical congenital cardiac disease to maintain ductal patency and facilitate pulmonary and systemic blood flow. In a related paradigm, PGE1 infusion has been used in situations of supra-systemic right ventricular pressures, including CDH, with the therapeutic intent to maintain ductal patency as a "pressure relief valve" to reduce the effective afterload on the right ventricle (RV), optimize cardiac function and support pulmonary and systemic blood flow. This paper reviews the current evidence for use of PGE1 in the CDH population and the opportunities for future investigations.